The present invention relates to storage-stable pesticide compositions and to methods for their preparation. In particular, the invention relates to storage-stable pesticide compositions containing azadirachtin as the active ingredient and an epoxide, preferably an epoxidized vegetable oil, as the stabilizing agent.
Extracts of the neem tree (Azadirachta indica) and the chinaberry tree (Melia azedarach) have long been known to have insecticidal activity (Natural Pesticides from the Neem Tree, Proc. 1st Int'l Neem Conf. 1980, 129 (H. Schmutterer, et al. eds. 1981)); Natural Pesticides from the Neem Tree and Other Tropical Plants, Proc. 2nd Int'l Neem Conf. 1983 (H. Schmutterer and K. R. S. Asher eds. 1984); Natural Pesticides from the Neem Tree and Other Tropical Plants, Proc. 3rd Int'l Neem Conf. 1986 (H. Schmutterer and K. R. S. Asher eds. 1987)). The active ingredient of the neem and chinaberry extracts, azadirachtin, is a limonoid of the tetranortriterpenoid type. Azadirachtin has been shown to be a potent insect growth regulator and feeding deterrent (Yamasaki, R. B., et al. (1987) J. Agric. Food Chem. 35:467-471).
Azadirachtin is a large and complex molecule. Its molecular weight is 720, and it has a number of reactive functional groups (including ester, epoxide, and vinyl ether moieties) which render the compound unstable under a variety of conditions. Azadirachtin is reported to decompose in the presence of acids, bases and water. E. D. Morgan, "Strategy in the Isolation of Insect Control Substances from Plants," Natural Pesticides from the Neem Tree, Proc. 1st Int'l Neem Conf. 1989, 45 (H. Schmutterer, et al. eds. 1981); S. V. Ley, et al. (1989) Tetrahedron 45:2143; S. V. Ley, "Synthesis of Insect Antifeedants," Pesticide Sci. Biotechnol., Proc. Int'l Cong. Pestic. Chem. 6th, 25-35 (R. Greenhalgh and T. R. Roberts, eds., 1987); J. A. Klocke, et al., U.S. Pat. No. 5,001,149; Fessenden and Fessenden, Organic Chemistry, 2nd Ed., 297,628 (1982); Morrison and Boyd, Organic Chemistry, 3rd Ed., 564, 675-684 (1974); G. F. Woods, Jr. (1955) Org. Syn. 3:470; M. Shiraishi and S. Terao (1983) J. C. S. Perkin I, 1591; and T. W. Greene, Protective Groups in Organic Synthesis, 21 (1981). In addition, J. B. Stokes and R. E. Redfern (1982) J. Environ. Sci. Health 17 (1):57-65, report rapid degradation of azadirachtin by heat and sunlight. K. Ermel, et al., Proc. 3rd Int'l Neem Conf. 1986, 171 (H. Schmutterer and K. R. S. Asher eds. 1987), report that azadirachtin rapidly decomposes in neem kernels stored at 60.degree. C. under humid, as compared to dry, conditions.
Chemical instability poses a serious impediment to the use of azadirachtin as a pesticidal agent. In short, the molecule tends to have a short shelf life in technical and formulated forms, as prepared by those skilled in the art. Short shelf life, in turn, poses problems for building and storing inventories, carrying product over from one year to the next, and guaranteeing product potency in the consumer's hands. To avert these problems, most chemical pesticide manufacturers require that their products have shelf lives of 2-3 years or more. Azadirachtin does not meet this criterion under most conditions. As such, means for improving the molecule's stability and, hence, its shelf life are of considerable commercial importance.
Storage-stable azadirachtin formulations and methods for preparing stable azadirachtin compositions have been proposed. U.S. Pat. No. 4,556,562 reports that the stability of azadirachtin in ethanol emulsions increases by diluting the concentration of azadirachtin to between 2000 and 4000 ppm and adjusting the pH to between 3.5 and 6.0. U.S. Pat. No. 5,001,146 discloses that azadirachtin stability is improved adjusting the concentration of polar aprotic solvent to at least 50% by volume and by decreasing water content to less than 15% by volume. Both of these prior art formulations were prepared to contain very low concentrations of azadirachtin (0.2-0.4% and 0.3% respectively). This fact places severe constraints on product composition, quality, utility, and consumer acceptance. Pesticides containing low concentrations of active ingredient must be applied at correspondingly high volumes in order for efficacy to be achieved. As such, high volumes of product must be manufactured, shipped, and stored. This factor adds to the costs incurred by manufacturers, distributors, and end users. Moreover, U.S. Pat. No. 5,001,146 teaches that azadirachtin stability depends upon the type of solvent employed, and that stability requires storage in certain enumerated aprotic and alcohol solvents. This factor constrains the use of a broader range of formulation ingredients, many of which are desirable from perspectives of product cost, product performance, user safety, and environmental compatibility.
It is known in the art that various antioxidants, inhibitors and scavengers can stabilize pesticidal compounds against spontaneous decomposition. It is further known in the art that addition of an epoxide compound to N-aminosulfenylated derivatives of carbofuran (U.S. Pat. No. 4,281,014), organophosphate (U.S. Pat. No. 3,867,526) and chlorinated hydrocarbon (U.S. Pat. No. 3,952,102) pesticides increases their shelf life. In general, however, different classes of chemical compounds require different stabilizers because mechanisms of decomposition vary from one pesticide class to the next (U.S. Pat. No. 4,281,014). Selection of a stabilizer is therefore an empirical process.
Azadirachtin is a biologically derived natural product obtained as a complex mixture of compounds by extraction from the seeds of the neem tree. It does not contain N-aminosulfenylated carbofuran, organophosphate or chlorinated hydrocarbon type functional groups found in the synthetic compounds previously mentioned. Nevertheless, it has been unexpectedly found that the stability of azadirachtin in solution is enhanced by the presence of an epoxide, preferably an epoxidized vegetable oil. Use of such an additive improves the stability of pesticide compositions containing a wide range of concentrations (including high concentrations) of azadirachtin. It also permits formulation in a broader range of solvents and other adjuvants that contribute to product performance and safety.